Background: Hyaluronidase (Hylase Dessau®) is a hyaluronic acid-metabolizing enzyme, which has been shown to loosen the extracellular matrix, thereby improving the diffusion of local anesthetics. Lower eyelid edema is a common post-interventional complication of cosmetic procedures performed in the lid region, such as the injection of hyaluronic acid fillers for tear-trough augmentation. The purpose of this study was to validate the efficacy of hyaluronidase in the management of lower eyelid edema. Methods: We performed a retrospective analysis with 20 patients with lower eyelid edema. Most patients (n = 14) presented with edema following hyaluronic acid injection (tear-trough augmentation), whereas the minority (n = 6) were treated due to idiopathic edema (malar edema or malar mounds). Patients were treated by local infiltration of approximately 0.2 ml to 0.5 ml of hyaluronidase (Hylase Dessau® 20 IU to 75 IU) per eyelid. Photographs were taken prior to and seven days after infiltration. Results: Hyaluronidase was found to reduce effectively and rapidly or resolve eyelid edema after a single injection. No relevant adverse effects were observed. However, it must be noted that a hyaluronidase injection may also dissolve injected hyaluronic acid fillers and may therefore negatively affect tear-trough augmentations. While the effects of a treatment for edema due to tear-trough augmentation were permanent, malar edema and malar mounds reoccurred within two to three weeks. Conclusion: The infiltration of hyaluronidase is rapid, safe and currently the only effective option for the management of eyelid edema. No relevant adverse effects were observed.